This application is to continue the University of Colorado Alcohol Research Center. This Center has been in formal existence since the NIAAA Centers program was re-initiated in 1977. Consistently the Center has utilized genetic techniques to provide animal models with which to unlock the secrets of the action of ethanol at a molecular level. As a corollary to these studies we have also utilized genetic techniques to investigate the effect of ethanol in human subjects and to investigate the role of genetics in human alcoholism as well. While these two areas are closely related, it has always been a guiding principle that animal genetic studies are valuable as tools to investigate fundamental actions of ethanol, whether or not the genetic polymorphisms so useful in animals exist in humans.